The objective of this proposal is to design and investigate an efficient transition metal-catalyzed enantioselective annulation process that involves intramolecular cross-coupling of sp2 C-H bonds with multiple bonds via C-H activation. This new asymmetric cyclization process can be accomplished by annulating an unsaturated olefin tether into an existing unsaturated ring in presence of catalytic quantities of chiral ruthenium or rhodium bidentate phosphine complexes. The products obtained from this annulation process can then be quickly and efficiently transformed into a variety of biologically active, homochiral natural products such as Liguhodgsonal, pyrrolizidines, indolizidines, and many other quinone alkaloids such as mitomycins and mitosenes having pronounced antibacterial and antitumor activity. Compared to other ring construction strategies, the proposed annulation process has several advantages including: application in catalytic enantioselective synthesis, coupling of unactivated multiple bonds, relative ease of preparation of substrates, use of a catalytic quantity of chiral ruthenium or rhodiurn complexes, and use of non-halogenated organic materials, thus reducing waste problems. Furthermore, current asymmetric annulation procedure would provide simple and efficient routes for the construction of homochiral, poly-substituted carbocycles and heterocycles. This new methodology, together with its features, may be a practical protocol for synthesis of pharmaceuticals and other biologically active compounds of medicinal interest.